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This article describes a robot walker based on a new single degree-of-freedom six-bar leg mechanism that provides rectilinear, non-rotating, movement of the foot. The walker is statically stable and requires only two actuators, one for each side, to provide effective walking movement on a flat surface. We use Curvature Theory to design a four-bar linkage with a flat-sided coupler curve and then adds a translating link so that walker foot follows this coupler curve in rectilinear movement. A prototype walker was constructed that weighs 1.6 kg, is 180 mm tall, and travels at 162 mm/s. This is an innovative legged robot that has a simple reliable design.
COVID-19 lockdowns increased the risk of mental health problems, especially for children with autism spectrum disorder (ASD). However, despite its importance, little is known about the protective factors for ASD children during the lockdowns.
Based on the Shanghai Autism Early Developmental Cohort, 188 ASD children with two visits before and after the strict Omicron lockdown were included; 85 children were lockdown-free, while 52 and 51 children were under the longer and the shorter durations of strict lockdown, respectively. We tested the association of the lockdown group with the clinical improvement and also the modulation effects of parent/family-related factors on this association by linear regression/mixed-effect models. Within the social brain structures, we examined the voxel-wise interaction between the grey matter volume and the identified modulation effects.
Compared with the lockdown-free group, the ASD children experienced the longer duration of strict lockdown had less clinical improvement (β = 0.49, 95% confidence interval (CI) [0.19–0.79], p = 0.001) and this difference was greatest for social cognition (2.62 [0.94–4.30], p = 0.002). We found that this association was modulated by parental agreeableness in a protective way (−0.11 [−0.17 to −0.05], p = 0.002). This protective effect was enhanced in the ASD children with larger grey matter volumes in the brain's mentalizing network, including the temporal pole, the medial superior frontal gyrus, and the superior temporal gyrus.
This longitudinal neuroimaging cohort study identified that the parental agreeableness interacting with the ASD children's social brain development reduced the negative impact on clinical symptoms during the strict lockdown.
The gold standard for hand hygiene (HH) while wearing gloves requires removing gloves, performing HH, and donning new gloves between WHO moments. The novel strategy of applying alcohol-based hand rub (ABHR) directly to gloved hands might be effective and efficient.
A mixed-method, multicenter, 3-arm, randomized trial.
Adult and pediatric medical-surgical, intermediate, and intensive care units at 4 hospitals.
Healthcare personnel (HCP).
HCP were randomized to 3 groups: ABHR applied directly to gloved hands, the current standard, or usual care.
Gloved hands were sampled via direct imprint. Gold-standard and usual-care arms were compared with the ABHR intervention.
Bacteria were identified on gloved hands after 432 (67.4%) of 641 observations in the gold-standard arm versus 548 (82.8%) of 662 observations in the intervention arm (P < .01). HH required a mean of 14 seconds in the intervention and a mean of 28.7 seconds in the gold-standard arm (P < .01). Bacteria were identified on gloved hands after 133 (98.5%) of 135 observations in the usual-care arm versus 173 (76.6%) of 226 observations in the intervention arm (P < .01). Of 331 gloves tested 6 (1.8%) were found to have microperforations; all were identified in the intervention arm [6 (2.9%) of 205].
Compared with usual care, contamination of gloved hands was significantly reduced by applying ABHR directly to gloved hands but statistically higher than the gold standard. Given time savings and microbiological benefit over usual care and lack of feasibility of adhering to the gold standard, the Centers for Disease Control and Prevention and the World Health Organization should consider advising HCP to decontaminate gloved hands with ABHR when HH moments arise during single-patient encounters.
We explored the utility of the standardized infection ratio (SIR) for surgical site infection (SSI) reporting in an Australian jurisdiction.
Retrospective chart review.
Statewide SSI surveillance data from 2013 to 2019.
Individuals who had cardiac bypass surgery (CABG), colorectal surgery (COLO), cesarean section (CSEC), hip prosthesis (HPRO), or knee prosthesis (KPRO) procedures.
The SIR was calculated by dividing the number of observed infections by the number of predicted infections as determined using the National Healthcare Safety Network procedure-specific risk models. In line with a minimum precision criterion, an SIR was not calculated if the number of predicted infections was <1.
A SIR >0 (≥1 observed SSI, predicted number of SSI ≥1, no missing covariates) could be calculated for a median of 89.3% of reporting quarters for CABG, 75.0% for COLO, 69.0% for CSEC, 0% for HPRO, and 7.1% for KPRO. In total, 80.6% of the reporting quarters, when the SIR was not calculated, were due to no observed infections or predicted infections <1, and 19.4% were due to missing covariates alone. Within hospitals, the median percentage of quarters during which zero infections were observed was 8.9% for CABG, 20.0% for COLO, 25.4% for CSEC, 67.3% for HPRO, and 71.4% for KPRO.
Calculating an SIR for SSIs is challenging for hospitals in our regional network, primarily because of low event numbers and many facilities with predicted infections <1. Our SSI reporting will continue to use risk-indexed rates, in tandem with SIR values when predicted number of SSI ≥1.
Social media and other technologies are reshaping communication and health.
This review addresses the relationship between social media use, behavioural health conditions and psychological well-being for youth aged <25 years.
A scoping review of 11 literature databases from 2000 to 2020 explored research studies in youth in five areas: clinical depression and anxiety, quantitative use, social media mode, engagement and qualitative dimensions and health and well-being.
Out of 2820 potential literature references, 140 met the inclusion criteria. The foci were clinical depression and anxiety disorders (n = 78), clinical challenges (e.g. suicidal ideation, cyberbullying) (n = 34) and psychological well-being (n = 28). Most studies focused on Facebook, Twitter, Instagram and YouTube. Few studies are longitudinal in design (n = 26), had comparison groups (n = 27), were randomised controlled trials (n = 3) or used structured assessments (n = 4). Few focused on different youth and sociodemographic populations, particularly for low-income, equity-seeking and deserving populations. Studies examined association (n = 120; 85.7%), mediating (n = 16; 11.4%) and causal (n = 4; 2.9%) relationships. Prospective, longitudinal studies of depression and anxiety appear to indicate that shorter use (≤3 h/day) and purposeful engagement is associated with better mood and psychological well-being. Depression may predict social media use and reduce perception of support. Findings provide families, teachers and providers ways to engage youth.
Research opportunities include clinical outcomes from functional perspective on a health continuum, diverse youth and sociodemographic populations, methodology, intervention and privacy issues. More longitudinal studies, comparison designs and effectiveness approaches are also needed. Health systems face clinical, training and professional development challenges.
Mitotic-inhibiting herbicides, like prodiamine and dithiopyr, are used to control annual bluegrass (Poa annua L.) preemergence in managed turfgrass; however, resistance to mitotic-inhibiting herbicides has evolved due to repeated applications of herbicide from a single mechanism of action. Three suspected resistant populations (R1, R2, and R3) were collected in Alabama and Florida and screened for resistance to prodiamine. Part of the α-tubulin gene was sequenced for known target-site mutations. Target-site mutations were reported in all three R populations, with each containing an amino acid substitution at position 239 from threonine to isoleucine (Thr-239-Ile). Previous research has indicated that the Thr-239-Ile mutation confers resistance to dinitroaniline herbicides in other species. Dose–response screens using prodiamine and dithiopyr were conducted and I50 values were calculated for R1, R2, and R3 using regression models based on seedling emergence. For prodiamine, I50 values for R1, R2, and R3 were 35.3, 502.7, and 91.5 g ai ha−1, respectively, resulting in 2.9-, 41.9-, and 7.6-fold resistance, respectively, when compared with a susceptible (S) population. For dithiopyr, I50 values for R1, R2, and R3 were 154.0, 114.2, and 190.1 g ai ha−1, respectively, resulting in 3.6-, 2.7-, and 4.5-fold resistance, respectively, when compared with an S population. When comparing I90 values with the highest labeled use rates, R2 had a 2.9-fold level of resistance to prodiamine, and R1, R2, and R3 had a 2.4-, 2.0-, and 3.2-fold levels of resistance to dithiopyr, respectively. This is the first report of a variable response in P. annua to prodiamine despite each R population possessing the same mutation.
Childhood is a crucial neurodevelopmental period. We investigated whether childhood reading for pleasure (RfP) was related to young adolescent assessments of cognition, mental health, and brain structure.
We conducted a cross-sectional and longitudinal study in a large-scale US national cohort (10 000 + young adolescents), using the well-established linear mixed model and structural equation methods for twin study, longitudinal and mediation analyses. A 2-sample Mendelian randomization (MR) analysis for potential causal inference was also performed. Important factors including socio-economic status were controlled.
Early-initiated long-standing childhood RfP (early RfP) was highly positively correlated with performance on cognitive tests and significantly negatively correlated with mental health problem scores of young adolescents. These participants with higher early RfP scores exhibited moderately larger total brain cortical areas and volumes, with increased regions including the temporal, frontal, insula, supramarginal; left angular, para-hippocampal; right middle-occipital, anterior-cingulate, orbital areas; and subcortical ventral-diencephalon and thalamus. These brain structures were significantly related to their cognitive and mental health scores, and displayed significant mediation effects. Early RfP was longitudinally associated with higher crystallized cognition and lower attention symptoms at follow-up. Approximately 12 h/week of youth regular RfP was cognitively optimal. We further observed a moderately significant heritability of early RfP, with considerable contribution from environments. MR analysis revealed beneficial causal associations of early RfP with adult cognitive performance and left superior temporal structure.
These findings, for the first time, revealed the important relationships of early RfP with subsequent brain and cognitive development and mental well-being.
The paper addresses the six-degree-of-freedom coupled control problem for spacecraft formation flying subject to actuator saturation and input quantisation whilst considering limited communication resources. Firstly, a novel event-triggered distributed observer without continuous communications is presented to recover the information of the virtual leader. Remarkably, by embedding a hyperbolic tangent function-based nonlinear term into the triggering condition, the event-based observer realises a more reasonable trigger threshold. Subsequently, an adding-a-power-integrator-based fixed-time control algorithm is proposed for the follower spacecraft. Further, the control scheme ingeniously compensates for the actuator saturation and the input quantisation problems without embedding auxiliary systems. Finally, numerical simulations are carried out to highlight the advantages of the theoretical results.
In masked priming lexical decision tasks in alphabetic or syllabic script languages, latencies are longer when a word target is primed by a higher frequency neighbor (e.g., blue–BLUR) than when primed by an unrelated word of equivalent frequency (e.g., care–BLUR) – an “inhibitory neighbor priming effect.” In contrast, Zhou et al. (1999) demonstrated facilitatory orthographic neighbor priming for two-character Chinese words (e.g., 华丽–华贵). However, Zhou et al. did not control for relative prime-target frequency, which has been shown to be important in experiments when examining languages with other scripts. In the present Experiment 1 word neighbor primes (e.g., 容易-容貌) produced an inhibitory neighbor priming effect when the prime was higher frequency than the target, paralleling effects in other script languages. In further experiments, paralleling those in other script languages, two-character targets primed by nonword neighbors (容待-容貌) or single constituent characters matching the target in either position (容-容貌) showed significant facilitation. These results suggest that lexical activation/competition processes for two-character Chinese words are reasonably similar to those for words in alphabetic/syllabic script languages.
People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown.
We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other.
Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone.
CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.
Children with fragile X syndrome (FXS) often avoid eye contact, a behavior that is potentially related to hyperarousal. Prior studies, however, have focused on between-person associations rather than coupling of within-person changes in gaze behaviors and arousal. In addition, there is debate about whether prompts to maintain eye contact are beneficial for individuals with FXS. In a study of young females (ages 6–16), we used eye tracking to assess gaze behavior and pupil dilation during social interactions in a group with FXS (n = 32) and a developmentally similar comparison group (n = 23). Participants engaged in semi-structured conversations with a female examiner during blocks with and without verbal prompts to maintain eye contact. We identified a social–behavioral and psychophysiological profile that is specific to females with FXS; this group exhibited lower mean levels of eye contact, significantly increased mean pupil dilation during conversations that included prompts to maintain eye contact, and showed stronger positive coupling between eye contact and pupil dilation. Our findings strengthen support for the perspective that gaze aversion in FXS reflects negative reinforcement of social avoidance behavior. We also found that behavioral skills training may improve eye contact, but maintaining eye contact appears to be physiologically taxing for females with FXS.
OBJECTIVES/GOALS: SGLT2i therapy is currently a cornerstone in heart failure with preserved ejection fraction (HFpEF) therapy. Similarly, H2S has been shown to be beneficial in preclinical models of heart failure. With this in mind, we sought to investigate the effects of the SGLT2i and H2S donor therapy alone or in combination in a rodent model of cardiometabolic HFpEF. METHODS/STUDY POPULATION: Male C57BL/6N mice (9 weeks of age) were fed a high fat, Western diet (HFD) and received L-NG-Nitro arginine methyl ester (L-NAME) in the drinking water (0.5 g/L) to induce HFpEF. At 5 weeks, animals were randomized to either control, H2S donor (SG-1002, 90 mg/kg/d, P.O), Empagliflozin (155 mg/L, P.O), or the combination of SG-1002 and Empagliflozin for an additional 5 weeks while being maintained on HFD and L-NAME. Echocardiography, left ventricular invasive LV and systemic hemodynamics, and exercise capacity testing were performed to assess cardiovascular disease severity. Fasted glucose, circulating triglyceride and cholesterol content were similarly measured to quantify key clinical metabolic parameters. H2S and its metabolite, sulfane sulfur, were quantified to assure adequate H2S donation. RESULTS/ANTICIPATED RESULTS: Administration of SG-1002 restored H2S and sulfane sulfur to normal circulating levels. All treatment groups exhibited similar improvements in LV diastolic dysfunction as measured by E/E’and LVEDP. Combination therapy significantly improved exercise capacity whereas the monotherapy groups did not. Treatment with SG-1002 decreased fasting glucose and circulating cholesterol while all treatment groups displayed decreased circulating triglycerides and body weight compared to HFpEF control. DISCUSSION/SIGNIFICANCE: These data indicate that restoring H2S or treatment with an SGLT2i in this preclinical HFpEF model attenuates pathology. Combination of both drugs exhibited greater benefit than either monotherapy in important HFpEF parameters such as exercise capacity. Further studies are underway to characterize the benefits observed from combination therapy.
OBJECTIVES/GOALS: Childhood psychiatric symptoms are highly comorbid. Their co-occurrence and association with negative life outcomes is partially explained by deficits in executive control, or processes enabling self-regulation. Here, we test a novel executive neural target in three fMRI tasks and its relevance to shared psychopathology. METHODS/STUDY POPULATION: We studied 60 children [15 F/45 M; mean age (SD)=11.6 years (1.62)] with diverse diagnoses including attention deficit disorder (n=26) and autism spectrum disorder (n=22). We extracted a latent general factor of psychopathology using principal component analyses applied to parent-report Child Behavior Checklist syndrome scores. Subjects completed 3 executive control fMRI probes, tapping adaptive control, working memory, and inhibition. Correlational psychophysiological interaction (cPPI) analysis measured correlations between executive control-related modulations of activity in 414 network-affiliated parcels. We selected parcels exhibiting control-related cross-network correlations as well as control-related activity across all tasks and tested them for association with psychopathology. RESULTS/ANTICIPATED RESULTS: cPPI connectivity matrices were thresholded and graphs were identified using the Network-Based Statistic toolbox (p90th percentile PC) as well as control-related activation (>10% activated voxels; p DISCUSSION/SIGNIFICANCE: Our results examine cross-network interactions between brain regions during 3 fMRI tasks and their role in explaining individual variation in psychopathology. As executive control links to both comorbidity and life outcomes, identifying the clinically-relevant neural correlates of controlled behavior may lead to transdiagnostic treatments.
OBJECTIVES/GOALS: Smoking is a well-established risk factor for lung cancer, but never smokers account for up to 25% of lung cancer cases. There is mounting evidence that lung cancer in never smokers is biologically distinct. We aim to characterize the genomic and immunologic features of lung adenocarcinoma in never smokers versus smokers. METHODS/STUDY POPULATION: We examined clinical, genomic, and bulk-RNA sequencing data from 499 patients in the TCGA lung adenocarcinoma cohort. Tumor mutation burden was analyzed using maftools (R package). Tumor immune characterization was completed using CIBERSORTx, a digital cytometry tool that uses single cell reference profiles to determine immune cell type frequencies from bulk-RNA sequencing data. Single cell reference profiles for 19 different immune cell types were constructed from sequencing of freshly resected lung tumor tissue from UCSF patients. Partitioning Around Medoids (PAM; R package) was used to identify distinct immune phenotypes based on immune cell composition. Fisher’s exact test was used to evaluate for associations between immune phenotypes and smoking status. RESULTS/ANTICIPATED RESULTS: Of the 499 TCGA lung adenocarcinoma patients, 75 were never smokers, 269 were female, and 246 were over the age of 65. Never smokers had lower tumor mutation burden and lower predicted neoantigen burden compared to smokers (p < 0.001). There was no difference in total tumor immune cell infiltration between never smokers and smokers. PAM yielded 2 distinct clusters/immune phenotypes. The first was enriched in M1 Macrophages, cytotoxic T Cells, helper T Cells, regulatory T Cells, and Plasma Cells. The second was enriched in plasmacytoid Dendritic Cells, M2 Macrophages, and exhausted cytotoxic T Cells. Never smoking status was associated with an increased odds of having the first immune phenotype (OR 1.95, 95% CI: 1.15 - 3.35) and this association was statistically significant (p = 0.0086). DISCUSSION/SIGNIFICANCE: Our findings suggest that never smokers have an immune phenotype that is distinct from that observed in smokers. The distinct immune characteristics we observed could explain clinical trial data suggesting immune checkpoint inhibitors are less effective in never smokers and hold implications for tailoring therapy.
Depression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network perspective yields a more complete insight than single outcome-single predictor models.
We used data from the Netherlands Study of Depression and Anxiety (N = 2498) and leveraged networks capturing associations between 30 depressive symptoms (Inventory of Depressive Symptomatology) and 46 metabolites. Analyses involved 4 steps: creating a network with Mixed Graphical Models; calculating centrality measures; bootstrapping for stability testing; validating central, stable associations by extra covariate-adjustment; and validation using another data wave collected 6 years later.
The network yielded 28 symptom-metabolite associations. There were 15 highly-central variables (8 symptoms, 7 metabolites), and 3 stable links involving the symptoms Low energy (fatigue), and Hypersomnia. Specifically, fatigue showed consistent associations with higher mean diameter for VLDL particles and lower estimated degree of (fatty acid) unsaturation. These remained present after adjustment for lifestyle and health-related factors and using another data wave.
The somatic symptoms Fatigue and Hypersomnia and cholesterol and fatty acid measures showed central, stable, and consistent relationships in our network. The present analyses showed how metabolic alterations are more consistently linked to specific symptom profiles.
Genetic profiling can validate pedigrees and reveal genetic diversity/inbreeding within populations. We have developed 12 autosomal microsatellite markers that can be used to DNA profile gibbon species. The panel generated full profiles for 39 individuals currently or previously housed at Twycross Zoo, UK, representing five species across three genera. The study is extending to a further approximate 100 samples, including three additional species, from captive populations across Europe. The panel’s cross-species utility allows for a single protocol to be used for all DNA profiling, avoiding the need for species-specific testing. In addition, the panel resolved an issue of uncertain paternity in a breeding group, with direct implications for group management and welfare. The loci reported here yielded profiles from blood, tissue and non-invasive hair samples. Positive impact on the viability and sustainability of captive breeding programmes is anticipated, by clarifying cryptic relatedness and informing future pairings. Potential exists for field application in investigating population dynamics, mating behaviours, relatedness and dispersal patterns, as well as assessing the impact of anthropogenic disturbances on the genetic architecture of populations. This established panel, effective across multiple gibbon species and genera, presents an affordable and expedient tool for research and captive management.
This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive.
A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors.
Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001).
Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer’s disease while considering the burden on the healthcare system.
Computerized-adaptive testing (CAT) may increase reliability or reduce respondent burden for assessing patient-reported outcomes compared with static short forms (SFs). We compared CAT versus SF administration of the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Pediatric measures in pediatric inflammatory bowel disease (IBD).
Participants completed 4-item CAT, 5- or 6-item CAT, and 4-item SF versions of the PROMIS Pediatric measures. We compared average T-scores, intra-class correlations (ICCs), floor and ceiling effects, and standard error of measurement (SEM) across forms, along with mean effect sizes between active versus quiescent IBD disease activity groups.
Average PROMIS T-scores across forms were <3 points (minimally important difference) of each other. All forms correlated highly with each other (ICCs ≥0.90) and had similar ceiling effects, but the CAT-5/6 had lower floor effects. The CAT-5/6 had lower SEM than the CAT-4 and SF-4, and the CAT-4 had a lower SEM than the SF-4. Mean effect sizes were similar across forms when contrasting disease activity groups.
The CAT and SF forms produced similar score results, but the CAT had better precision and lower floor effects. Researchers should consider PROMIS pediatric CAT if they anticipate that their sample will skew toward symptom extremes.
The coronavirus disease 2019 (COVID-19) pandemic has disproportionately impacted Black, indigenous, and people of color (BIPOC). Equitable access to therapeutics is key to addressing health disparities. We established a monoclonal infusion program in the emergency department of a safety-net hospital. Our program successfully reached underserved BIPOC communities and was sustained throughout the pandemic.
As a typical plasma-based optical element that can sustain ultra-high light intensity, plasma density gratings driven by intense laser pulses have been extensively studied for wide applications. Here, we show that the plasma density grating driven by two intersecting driver laser pulses is not only nonuniform in space but also varies over time. Consequently, the probe laser pulse that passes through such a dynamic plasma density grating will be depolarized, that is, its polarization becomes spatially and temporally variable. More importantly, the laser depolarization may spontaneously take place for crossed laser beams if their polarization angles are arranged properly. The laser depolarization by a dynamic plasma density grating may find application in mitigating parametric instabilities in laser-driven inertial confinement fusion.